crossing96/oncoscreening huggingface dataset:
Expression analysis of VEGF-A and VEGF-B: relationship with clinicopathological parameters in bladder cancer.	The present investigation was conducted first to determine whether correlation exists between VEGF-A and -B mRNA levels and clinicopathological parameters and to assess their prognostic value in bladder cancer, then to clarify the expression level and biological significance of VEGF-A isoforms. Total RNA was isolated from 37 specimens of bladder cancer. Northern blot analysis revealed that VEGF-B mRNA was not expressed either in normal urothelium or in bladder cancer and detected three VEGF-A transcripts of 5.2, 4.5 and 1.7 kb in length, respectively. The VEGF-A transcript levels were greater in cancer tissues than in normal urothelium. They were significantly higher in pT2-T4 than in pTa and pT1 urothelial tumors and thus, were correlated to the pathologic stage. Contrary to the 4.5 kb transcript, elevated expression of the 5.2 and 1.7 kb transcripts was correlated with the histologic grade and the presence of carcinoma in situ. Patients with higher VEGF-A mRNA levels had a significantly shorter survival without progression compared to those with lower levels. Three VEGF-A splice variants were detected by southern blotting namely, VEGF121, 165 and 189. The expression intensity of each isoform was evaluated by quantitative real-time RT-PCR in 20 new fresh frozen recent tumors. VEGF121 and VEGF165 were expressed at the similar level. On the contrary, they were significantly more expressed than VEGF189 (p<0.05). The three isoforms were higher expressed in pT2 bladder cancers than in pTa tumors (p<0.05). There was only a significant correlation between the increased expression level of VEGF121 and 165 and the histological grade of the lesion (p<0.05). To conclude, VEGF-A mRNA level is a potential prognostic indicator of progression in bladder cancer as well as the expression level of the different VEGF-A splice variants.	bladder
Activation of NFAT signal by p53-K120R mutant.	The tumor suppressor p53 is activated by phosphorylation and/or acetylation. We constructed 14 non-phosphorylated, 11 phospho-mimetic, and 1 non-acetylated point p53 mutations and compared their transactivation ability in U-87 human glioblastoma cells by the luciferase reporter assay. Despite mutations at the phosphorylation sites, only the p53-K120R and p53-S9E mutants had marginally reduced activities. On the other hand, the Nuclear factor of activated T-cells (NFAT)-luciferase reporter was more potently activated by p53-K120R than by wild-type p53 and other mutants in glioblastoma, hepatoma and esophageal carcinoma cells. This suggests that acetylation at Lys-120 of p53 negatively regulates a signaling pathway leading to NFAT activation.	bladder
Histopathologic features and clinical outcomes in 71 cases of bladder diverticula.	CONTEXT: Bladder diverticula often come to clinical attention when complications or malignancy occur, although limited information is available regarding histopathologic features and clinical outcomes. OBJECTIVE: To identify the morphologic findings, neoplastic subtypes, and clinical outcomes by reviewing all bladder diverticula that underwent pathologic sampling for primary diverticular processes at the Cleveland Clinic. DESIGN: Hematoxylin-eosin slides from 71 cases of bladder diverticula were reviewed. Clinicopathologic features and patient outcomes were obtained from a retrospective review of patient records. RESULTS: Patient ages ranged from 1 to 81 years (mean, 55 years), and the ratio of males to females was 68:3. Diverticular size ranged from 1 to 18 cm (mean, 5.3 cm) and often involved the lateral walls (38/71; 54%). Neoplastic changes were present in half of cases (36/71; 51%), including both noninvasive (16/36; 44%) and invasive (20/ 36; 56%) carcinoma. Of the invasive carcinomas, less-common subtypes included small cell carcinoma (n = 3), squamous cell carcinoma (n = 2), and adenocarcinoma (n = 1); 9 cases were pT1 (45%) and 11 cases were pT3 (55%). Follow-up for patients with benign findings demonstrated no subsequent neoplastic bladder disease. Patient follow-up for neoplastic diverticula (median, 27 months) demonstrated 4 cases of local recurrence and 3 cases of subsequent metastases. Of 9 patients with pT1 disease, only 1 patient (11%) developed subsequent metastases, whereas patients with pT3 disease demonstrated a higher rate of both local recurrence (3/11; 27%) and subsequent metastases (2/11; 18%). CONCLUSIONS: Patients with invasive carcinoma in diverticula have an increased frequency of less-common bladder cancer subtypes, and those with pT3 disease are at increased risk for subsequent progression.	bladder
Quantitative exposure to metalworking fluids and bladder cancer incidence in a cohort of autoworkers.	Occupations with mineral oil exposure have been associated with bladder cancer in population-based case-control studies. The authors report results from the first cohort study to examine bladder cancer incidence in relation to quantitative exposures to metalworking fluids (MWFs), based on 21,999 male Michigan automotive workers, followed from 1985 through 2004. Cox regression was used to estimate hazard ratios based on categorical exposure variables for straight, soluble, and synthetic MWFs, as well as duration of exposure to ethanolamines and nitrosamines. Penalized splines were also fit to estimate the functional form of the exposure-response relation. Increased bladder cancer risk was associated with straight MWFs but not with any other exposure. The hazard ratio increased with cumulative exposure to a maximum of 2-fold observed at 75 mg/m(3)-year straight MWF exposure (lagged 20 years). Calendar time windows relevant to polycyclic aromatic hydrocarbon exposure were examined but could not be distinguished from the lagged (10-, 20-year) metrics. No association was observed between any exposure and incident lung cancer, suggesting that smoking is unlikely to confound the associations observed here. The quantitative relation with straight MWFs strengthens the evidence for mineral oils as a bladder carcinogen.	bladder
Significance of 5-fluorouracil-related enzyme activities in predicting sensitivity to 5-fluorouracil in bladder carcinoma.	BACKGROUND: The association between 5-fluorouracil (5-FU)-related enzyme activity and the sensitivity of bladder urothelial carcinoma (BUC) to 5-FU were investigated, and methods to improve 5-FU sensitivity were analyzed. MATERIALS AND METHODS: Tumor specimens were obtained from 127 patients. Orotate phosphoribosyl transferase (OPRT) activity was analyzed by the paper disc method and thymidine phosphorylase and dihydropyrimidine dehydrogenase (DPD) activities were measured by ELISA. 5-FU sensitivity was assessed in 99 cases by an in vitro chemosensitivity test. RESULTS: A significant positive correlation between OPRT activity level and the sensitivity of BUC to 5-FU was identified. Moreover, the combination of 5-FU and 5-chloro-2,4-dihydroxypyrimidine significantly enhanced 5-FU sensitivity in BUC, particularly in cases showing higher DPD activity. CONCLUSION: OPRT was the most important enzyme in predicting sensitivity to 5-FU in BUC. These results may have implications for tailor-made medication using 5-FU-related compounds as postoperative adjuvant chemotherapy in BUC patients.	bladder
Management of the first recurrence of T1G3 bladder cancer: does intravesical chemotherapy deserve a chance?	OBJECTIVE: Is there a role for intravesical chemotherapy in a patient who has a first recurrence of a T1G3 bladder cancer? MATERIALS AND METHODS: American and European guidelines are checked for their advise, and recent literature on this topic is reviewed to critically test the advice and look for potential alternative strategies in this particular case. RESULTS: Guidelines indicate that a patient with a pT1G3 tumor should initially receive BCG intravescial therapy, although cystectomy can be considered. In case of a recurrence, cystectomy is the treatment of choice. Although several new drugs and strategies are under development and in clinical research, there is only experience to some degree in BCG failing patients with thermochemotherapy, with promising results. CONCLUSIONS: In a patient with a recurrence of T1G3 bladder cancer after BCG therapy, progression and subsequent cancer death is the threat. Guideline standard is radical surgery. Alternative possibilities are still limited.	bladder
Novel approach of laparoscopic transperitoneal en bloc resection of urachal tumor and umbilectomy with a comparison of various techniques.	Urachal carcinoma is a rare cancer that accounts for less than 1% of all bladder cancers. Surgical resection remains the mainstay of treatment. With partial cystectomy, long-term survival is possible following complete resection of the tumor. In this paper, we describe a novel approach of laparoscopic en bloc partial cystectomy and umbilectomy. We emphasize the importance of complete resection of the tumor and umbilicus and prevention of tumor spillage during the procedure. The literature is also reviewed for the comparison of various laparoscopic techniques.	bladder
Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder.	PURPOSE: Mutational activation of the MAP kinase pathway is frequently found in many types of cancer. Recently, activating mutations in the BRAF gene, an important activator of this pathway, have been described in several tumor types including melanoma, colorectal and papillary thyroid cancer. The most frequent mutation in exon 15 (V600E) as well as several other mutations within exons 11 and 15 result in constitutive activation of the oncoprotein. MATERIALS AND METHODS: Our study aimed to investigate BRAF mutations in 30 human bladder tumors and their adjacent normal tissues. The V600E mutation was screened by PCR/RFLP and exons 11, 14 and 15 of BRAF including intron-exon boundaries were sequenced. RESULTS: We detected two tumor specimens bearing two different mutations, both of which were found in exon 15. One sample showed the T1799A (V600E) and the other the G1798T (V600L) mutation. The first specimen was stage pT1a and grade II, whereas the second was stage pT2b and grade III. No mutations within the coding region of exons 11, 14, 15 and the intron-exon junctions for the remaining samples were found. CONCLUSIONS: Our results suggest that involvement of BRAF mutations in the development of transitional cell carcinoma of the bladder is infrequent.	bladder
Effects on biological behavior of bladder carcinoma T24 cells via silencing DNMT1 and/or DNMT3b with shRNA in vitro.	In this study, RNA interference technique was employed to silence the expression of DNMT1 and/or DNMT3b in human bladder cancer T24 cells. The expression levels of their mRNA and protein were greatly decreased by up to 75% and 65% respectively after T24 cells were transfected with lipofectamine2000 for 72 h, indicating RNA interference is an effective tool in gene knockdown. Proliferation and apoptosis of T24 cells were detected by MTT, and annexin-V-FITC and propidium iodide staining flow cytometry, respectively. It was found that loss of the DNMT1 or DNMT3b expression could inhibit the cell growth and promote the cell apoptosis to some extent. However, combined treatment with shRNA targeting both DNMT1 and DNMT3b mRNA could obviously enhance the above effects. It was concluded that simultaneously silencing both genes could result in strong suppressing effect on tumor proliferation and promoting cell apoptosis than separate use, suggesting combined use of DNMT1 and DNMT3b can achieve a synergistic effect in the CpG island methylation in human bladder tumorigenesis.	bladder
Granulomatous epididymo-orchitis, a rare complication of intravesical bacillus Calmette-Guérin therapy for urothelial cancer.	Only a few cases of tuberculous epididymo-orchitis after bacillus Calmette-Guérin (BCG) therapy have been published. This report presents a case of granulomatous epididymo-orchitis after intravesical BCG therapy in a patient presenting with pain and unilateral swelling of the scrotal content. This complication should always be considered when a patient presents with these symptoms after BCG therapy. Isoniazid may be used as a first choice of treatment.	bladder
Urinary calreticulin in the diagnosis of bladder urothelial carcinoma.	OBJECTIVES: To evaluate the potential suitability of calreticulin (CRT) as a urinary marker for bladder cancer. METHODS: Urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1; n = 109), urological patients without urothelial carcinoma (Group 2; n = 60), and non-urological patients (Group 3; n = 40). We developed an enzyme-linked immunosorbent assay (ELISA) procedure using commercially available anti-CRT mono/polyclonal antibodies, and then measured the concentration of urinary CRT. RESULTS: Urinary CRT concentration of group 1 was significantly higher than group 2 and 3 (Mann-Whitney U-test, P < 0.001). Groups 2 and 3 were joined together and considered as a non-bladder cancer group (n = 100), and a cutoff value (2.85 ng/mL) was determined using receiver operating characteristic (ROC) analysis. The sensitivity, specificity, and the area under the curve were 67.9%, 80.0%, and 0.742, respectively. The overall sensitivity of voided urine cytology (VUC) was 39.0% (n = 105), and the sensitivity of urinary CRT was significantly superior to VUC (McNemar test, P < 0.001). Higher sensitivity was observed especially in Ta, G1-2, and <or=3 cm tumors. CONCLUSIONS: Urinary CRT may be useful for diagnosis of bladder urothelial cancer. However, given that its specificity is relatively low, further evaluation in larger series is needed to define its clinical usefulness.	bladder
A single-institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to bacille Calmette-Guérin therapy.	OBJECTIVE: To analyse the durability of response for patients with non-muscle-invasive bladder cancer (NMIBC) refractory to bacille Calmette-Guérin (BCG) therapy and treated with intravesical docetaxel in a combined induction and maintenance regimen. PATIENTS AND METHODS: A previous phase I trial showed docetaxel to be safe for intravesical therapy, with no systemic absorption and minimal toxicity after six weekly instillations for patients with BCG-refractory NMIBC. In that trial, docetaxel gave a 56% complete response (CR) rate at 12 weeks, but the durability was only 22%. Thus a second group of patients was treated with a 6-week induction and then given monthly maintenance therapy with intravesical docetaxel. Thirteen patients with BCG-refractory Ta, T1, or Tis transitional cell carcinoma were treated. Induction therapy was administered as six weekly intravesical instillations of 75 mg followed by single-dose monthly maintenance therapy for nine additional instillations in patients who had a CR. The initial response at 12 weeks from the start of induction therapy was evaluated by cystoscopy with biopsy, and urine cytology. The follow-up consisted of quarterly cystoscopy with biopsy and cytology, and periodic imaging. RESULTS: The median follow-up was 13 months; 10 of 13 patients had a CR after induction, and six have remained disease-free during the follow-up. Of those in who the treatment failed, six had transurethral resection of the tumour and one a cystectomy. All 10 initial responders completed at least three instillations of maintenance therapy to date (median nine instillations), of whom six have remained recurrence-free. CONCLUSION: Monthly maintenance therapy with intravesical docetaxel appears to extend the durability of response to induction treatment for a selected group of patients with BCG-refractory NMIBC, and might decrease the overall risk of recurrence in high-risk NMIBC.	bladder
Mouse orthotopic models for bladder cancer research.	Bladder cancer is a common malignancy in the urinary tract. Despite different therapeutic options, recurrence and progression of urothelial carcinoma after treatment is not uncommon. Novel therapeutic options of bladder cancer are urgently needed. The preclinical evaluation of new treatments requires an animal tumour model that mimics the human counterpart. To date, various animal orthotopic bladder cancer models have been described, but the reported rate of tumour 'take' is 30-100%. The establishment of reliable and reproducible animal models remains an ongoing challenge. We review different kinds of mouse models of orthotopic bladder cancer used in urothelial cancer studies, the methods of implantation, and the reported rate of tumour take. Significant progress has been made recently in noninvasive small animal-imaging in tumour models. It is now possible for researchers to investigate the effects of studied agents by monitoring of in vivo tumour growth directly and noninvasively, as well as measuring a wide range of tumour-related variables in small animals. We summarize the recent development in small-animal imaging for tumour detection and quantification.	bladder
Development of a multiplex quantitative PCR signature to predict progression in non-muscle-invasive bladder cancer.	In bladder cancer, clinical grade and stage fail to capture outcome. We developed a clinically applicable quantitative PCR (QPCR) gene signature to predict progression in non-muscle-invasive bladder cancer. Comparative metaprofiling of 12 DNA microarray data sets (comprising 631 samples and 241,298 probe sets) identified 96 genes, which showed differential expression in seven clinical outcome categories, or were identified as outliers, historic markers, or housekeeping genes. QPCR was done to determine mRNA expression from 96 bladder tumors. Fifty-seven genes differentiated T2 from non-T2 tumors (P < 0.05). Principal components analysis and Cox regression models were used to predict probability of T2 progression for non-T2 patients, placing them into high- and low-risk groups based on their gene expression. At 2 years, high-risk patients exhibited greater T2 progression (45% for high-risk patients versus 12% for low-risk patients; P = 0.003, log-rank test). This difference remained significant within T1 tumors (61% for high-risk patients versus 22% for low-risk patients; P = 0.02) and Ta tumors (29% for high-risk patients versus 0% for low-risk patients; P = 0.03). The best multivariate Cox model included stage and gender, and this signature provided predictive improvement over both (P = 0.002, likelihood ratio test). Immunohistochemistry was done for two genes in the signature not previously described in bladder cancer, ACTN1 and CDC25B, corroborating their up-regulation at the protein level with disease progression. Thus, we identified a 57-gene QPCR panel to help predict progression of non-muscle-invasive bladder cancers and delineate a systematic, generalizable approach to converting microarray data into a multiplex assay for cancer progression.	bladder
High throughput molecular diagnostics in bladder cancer - on the brink of clinical utility.	An enormous body of high-throughput genome-wide data, in particular gene expression data, has been gathered from roughly all human cancer forms in the past 10 years. This has widely increased our understanding of the cancer disease and its molecular changes and pathways, with a large contribution from studies of cancer cell lines and functional genomics. In the last three years, the focus has been moved to clinical outcome parameters as recurrence, progression, metastasis and treatment response. The huge variability of molecular changes and poor availability of samples have hampered progress in the field of epithelial cancer (carcinoma). However, independent validation of molecular profiles across high-throughput platforms, methods, laboratories and cancer populations has recently been successfully performed for several carcinomas, including bladder cancer. Application of advanced bioinformatics to identify interrelated pathways has revealed common signatures predictive of molecular subgroups, improving histopathological diagnosis, and ultimately outcome prediction. With breast cancer leading the field, colorectal, bladder and renal cell carcinomas well on their way, and many others soon to join, the era of clinical applications of high-throughput molecular methods in cancer lies closely ahead. This review illustrates in detail the perspectives for the management of bladder cancer.	bladder
Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice.	Overexpression of FGF receptor 3 (FGFR3) is implicated in the development of t(4;14)-positive multiple myeloma. While FGFR3 is frequently overexpressed and/or activated through mutations in bladder cancer, the functional importance of FGFR3 and its potential as a specific therapeutic target in this disease have not been elucidated in vivo. Here we report that inducible knockdown of FGFR3 in human bladder carcinoma cells arrested cell-cycle progression in culture and markedly attenuated tumor progression in xenografted mice. Further, we developed a unique antibody (R3Mab) that inhibited not only WT FGFR3, but also various mutants of the receptor, including disulfide-linked cysteine mutants. Biochemical analysis and 2.1-A resolution crystallography revealed that R3Mab bound to a specific FGFR3 epitope that simultaneously blocked ligand binding, prevented receptor dimerization, and induced substantial conformational changes in the receptor. R3Mab exerted potent antitumor activity against bladder carcinoma and t(4;14)-positive multiple myeloma xenografts in mice by antagonizing FGFR3 signaling and eliciting antibody-dependent cell-mediated cytotoxicity (ADCC). These studies provide in vivo evidence demonstrating an oncogenic role of FGFR3 in bladder cancer and support antibody-based targeting of FGFR3 in hematologic and epithelial cancers driven by WT or mutant FGFR3.	bladder
Epigenetic biomarkers in urothelial bladder cancer.	Bladder cancers comprise heterogeneous cell populations, and numerous factors are likely to be involved in dictating recurrence, progression and patient survival. While several molecular markers that are used to evaluate the development and prognosis of bladder cancer have been studied, the limited value of these established markers has created the need for new molecular indicators of bladder cancer prognosis. Of particular interest is the silencing of tumor-suppressor genes by epigenetic alteration. Recent progress in understanding epigenetic modification and gene silencing has led to new opportunities for the understanding, detection, treatment and prevention of cancer. Moreover, epigenetic silencing of tumor-suppressor genes is interesting from a clinical standpoint, because of the possibility of reversing epigenetic changes and restoring gene function in a cell. This review focuses on the prognostic relevance of epigenetic markers in bladder cancer.	bladder